Mononuclear phagocytes are important hosts for HIV-1, playing key roles in the dissemination of the virus and the pathogenesis of AIDS. These studies focus on defining phenotypic and functional changes of mononuclear phagocytes from AIDS patients and in normal monocytes following HIV-1 infection in vitro. Based on the emerging evidence that monocytes are central to the evolution of AIDS, studies are also directed at exploring potential antiviral therapies targeted at this population. Recent evidence indicates that monocytic cells infected with HIV-1 in vitro secrete TGF- beta and furthermore, HIV-1 infected cells of monocytic lineage which produce TGF-beta have been identified in tissues of AIDS patients. Identification of TGF-beta, a cytokine with numerous immunoregulatory functions in HIV-1-infected brain tissues implicates this cytokine in HIV encephalopathy. Moreover, the ability of HIV-1 infected mononuclear phagocyte products to modulate astrocyte functions suggests a pivotal role for the monocytic cells once they reach the CNS both in the initiation and perpetuation of the intracerebral pathology characteristic of AIDS. Because of the role of mononuclear phagocytes in HIV infection, studies were undertaken to target antiviral agents to this population. In this regard, an IL-2-toxin fusion conjugate has been shown to selectively bind to HIV-infected, IL-2 receptor positive monocytes, thereby eliminating this population. Continuing studies to elucidate phenotypic and functional abnormalities in these cells may provide new avenue of therapy.